Phase 3 N=120 Randomized Treatment

A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients Without Inhibitors

Hemophilia A · Hemophilia B

Bottom Line

View on ClinicalTrials.gov: NCT03417245 ↗

Enrolled (actual)

120

Serious AEs

8.4%

Results posted

Feb 2022

Primary outcome: Primary: Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period — 30.991; 3.133 episodes per participant per year — p=<0.0001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: fitusiran (Drug); factor concentrates (Drug)
Age: Pediatric, Adult, Older Adult · 12+ yrs
Sex: Male
Sponsor: Genzyme, a Sanofi Company
Primary completion: Jan 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period	30.991; 3.133	<0.0001 sig
PRIMARY Observed Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period	21.8; 0.0	—
SECONDARY Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Treatment Period	31.444; 4.092	<0.0001 sig
SECONDARY Observed Annualized Bleeding Rate (ABR) for Treated Bleeds During the Treatment Period	25.2; 1.8	—
SECONDARY Estimated Annualized Spontaneous Bleeding Rate for Treated Bleeds During the Efficacy Period	22.036; 1.825	<0.0001 sig
SECONDARY Observed Annualized Spontaneous Bleeding Rate for Treated Bleeds During the Efficacy Period	16.1; 0.0	—
SECONDARY Estimated Annualized Joint Bleeding Rate for Treated Bleeds During the Efficacy Period	23.413; 2.282	<0.0001 sig
SECONDARY Observed Annualized Joint Bleeding Rate for Treated Bleeds During the Efficacy Period	15.9; 0.0	—
SECONDARY Health-related Quality of Life (HRQOL): Change From Baseline in Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Score at Month 9	-3.32; -23.07	<0.0001 sig
SECONDARY Health-related Quality of Life (HRQOL): Change From Baseline in Haem-A-QOL Total Score at Month 9	-2.62; -9.68	=0.0011 sig
SECONDARY Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Onset Period	33.389; 10.805	—
SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	18; 62; 5; 5	—

Summary

Primary Objective: -To evaluate the efficacy of fitusiran compared to on-demand treatment with factor concentrates, as determined by the frequency of bleeding episodes. Secondary Objectives: * To evaluate the efficacy of fitusiran compared to on-demand treatment with factor concentrates, as determined by: * The frequency of spontaneous bleeding episodes. * The frequency of joint bleeding episodes. * Health-related quality of life (HRQOL) in participants >=17 years of age. * To determine the frequency of bleeding episodes during the onset period. * To determine the safety and tolerability of fitusiran.

Eligibility Criteria

Inclusion Criteria

Males, >=12 years of age.
Severe hemophilia A or B without inhibitors.
Severity confirmed by a central laboratory where FVIII level was less than (<) 1 percent (%) or Factor IX (FIX) level was less than or equal to (<=) 2% at Screening.
On-demand use of factor concentrate to manage bleeding episodes for at least the last 6 months prior to Screening, and meet each of the following criterion:
Nijmegen modified Bethesda assay inhibitor titer of <0.6 Bethesda units per milliliter (BU/mL) at Screening.
No use of Bypassing agents to treat bleeding episodes for at least the last 6 months prior to Screening.
No history of immune tolerance induction therapy within the last 3 years prior to Screening.
A minimum of 6 bleeding episodes requiring factor concentrate treatment within the last 6 months prior to Screening.
Willing and complied with the study requirements and to provide written informed consent and assent.

Exclusion Criteria

Known co-existing bleeding disorders other than hemophilia A or B, i.e., Von Willebrand's disease, additional factor deficiencies, or platelet disorders.
Antithrombin (AT) activity <60% at Screening.
Co-existing thrombophilic disorder.
Clinically significant liver disease.
Active hepatitis C virus infection.
HIV positive with a cluster of differentiation-4 count of <200 cells/microliter.
History of arterial or venous thromboembolism.
Inadequate renal function.
History of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-Acetylgalactosamine (GalNAc).
History of intolerance to SC injection(s).
Any other conditions or comorbidities that would make the participant unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgment.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03417245). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.